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La frecuencia de la homocigosidad genómica de la línea germinal asociada con los casos de cáncer
Guillaume Assié1, Thomas LaFramboise, Petra Platzer
1Genomic Medicine Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
JAMA
|March 28, 2008
Resumen
El aumento de la homocigosidad de la línea germinal en loci específicos está relacionado con mayores frecuencias de pérdida de heterocigosidad (LOH) en tumores sólidos. Este hallazgo sugiere un papel para la homocigosidad de la línea germinal en la predisposición y progresión del cáncer.
Área de la Ciencia:
- Genética La genética.
- Oncología Oncología.
- Investigación del cáncer Investigación del cáncer.
Sus antecedentes:
- El cáncer es una enfermedad compleja influenciada por factores genéticos, incluyendo predisposiciones hereditarias y mutaciones adquiridas.
- La pérdida de heterocigosidad (LOH) es un evento común en el cáncer, pero las observaciones anecdóticas sugirieron un papel potencial para la homocigosidad de la línea germinal en la predisposición al cáncer.
Objetivo del estudio:
- Investigar la frecuencia de la homocigosidad de la línea germinal en pacientes con tumores sólidos en comparación con controles sanos.
- Para determinar si el aumento de la homocigosidad de la línea germinal se asocia con la LOH en los tejidos cancerosos.
Principales métodos:
- Se analizó la línea germinal y el ADN tumoral de 385 pacientes con carcinomas de mama, próstata y cabeza y cuello para LOH utilizando análisis de microsatélites de genoma completo.
- Se compararon las frecuencias de homocigosidad de la línea germinal en loci específicos entre pacientes con cáncer y controles.
- Las frecuencias somáticas de LOH se evaluaron en los loci con alta homocigosidad de la línea germinal.
Principales resultados:
- Se observaron frecuencias significativamente más altas de homocigosidad de la línea germinal en pacientes con cáncer en comparación con los controles en 16 loci comunes (P < .001).
- En pacientes con cáncer que eran heterocigotos de la línea germinal en estos loci, las frecuencias de LOH fueron más altas (58%) en comparación con otros marcadores (50%) (P < .001).
- Estas asociaciones fueron validadas en un conjunto de datos independiente de carcinomas pulmonares y en todo el genoma.
Conclusiones:
- El aumento de la homozigosidad de la línea germinal en loci específicos es un hallazgo recurrente en múltiples tipos de tumores sólidos.
- La heterocigosidad de la línea germinal en estos loci de alta homocigosidad se asocia con un aumento de la LOH en los carcinomas correspondientes.
- Estos hallazgos ponen de relieve un papel potencial de la homocigosidad de la línea germinal en la predisposición y el desarrollo del cáncer.
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